Reza Golestani1, Mahmoud Razavian1, Lei Nie1, Jiasheng Zhang1, Jae-Joon Jung1, Yunpeng Ye1, Michelle de Roo1, Koen Hilgerink1, Chi Liu1, Simon P Robinson1, Mehran M Sadeghi2. 1. From the Section of Cardiovascular Medicine and Cardiovascular Research Center (R.G., M.R., L.N., J.Z., J.-J.J., Y.Y, M.d.R., K.H., M.M.S.), Department of Diagnostic Radiology (C.L.), Yale University School of Medicine, New Haven, CT; VA Connecticut Healthcare System, West Haven (R.G., M.R., L.N., J.Z., J.-J.J., Y.Y, M.d.R., K.H., M.M.S.); and Lantheus Medical Imaging, North Billerica, MA (S.P.R.). 2. From the Section of Cardiovascular Medicine and Cardiovascular Research Center (R.G., M.R., L.N., J.Z., J.-J.J., Y.Y, M.d.R., K.H., M.M.S.), Department of Diagnostic Radiology (C.L.), Yale University School of Medicine, New Haven, CT; VA Connecticut Healthcare System, West Haven (R.G., M.R., L.N., J.Z., J.-J.J., Y.Y, M.d.R., K.H., M.M.S.); and Lantheus Medical Imaging, North Billerica, MA (S.P.R.). Mehran.sadeghi@yale.edu.
Abstract
BACKGROUND: Abdominal aortic aneurysm (AAA) rupture risk is currently determined based on size and symptoms. This approach does not address the rupture risk associated with small aneurysms. Given the role of matrix metalloproteinases (MMPs) in AAA weakening and rupture, we investigated the potential of MMP-targeted imaging for detection of aneurysm biology and prediction of outcome in a mouse model of AAA with spontaneous rupture. METHODS AND RESULTS: Fifteen-week-old mice (n=66) were infused with angiotensin II for 4 weeks to induce AAA. Saline-infused mice (n=16) served as control. The surviving animals underwent in vivo MMP-targeted micro-single photon emission computed tomographic/computed tomographic imaging, using RP805, a technetium-99m-labeled MMP-specific tracer, followed by ex vivo planar imaging, morphometry, and gene expression analysis. RP805 uptake in suprarenal aorta on micro-single photon emission computed tomographic images was significantly higher in animals with AAA when compared with angiotensin II-infused animals without AAA or control animals. CD68 expression and MMP activity were increased in AAA, and significant correlations were noted between RP805 uptake and CD68 expression or MMP activity but not aortic diameter. A group of angiotensin II-infused animals (n=24) were imaged at 1 week and were followed up for additional 3 weeks. RP805 uptake in suprarenal aorta at 1 week was significantly higher in mice that later developed rupture or AAA. Furthermore, tracer uptake at 1 week correlated with aortic diameter at 4 weeks. CONCLUSIONS: MMP-targeted imaging reflects vessel wall inflammation and can predict future aortic expansion or rupture in murine AAA. If confirmed in humans, this may provide a new paradigm for AAA risk stratification.
BACKGROUND:Abdominal aortic aneurysm (AAA) rupture risk is currently determined based on size and symptoms. This approach does not address the rupture risk associated with small aneurysms. Given the role of matrix metalloproteinases (MMPs) in AAA weakening and rupture, we investigated the potential of MMP-targeted imaging for detection of aneurysm biology and prediction of outcome in a mouse model of AAA with spontaneous rupture. METHODS AND RESULTS: Fifteen-week-old mice (n=66) were infused with angiotensin II for 4 weeks to induce AAA. Saline-infused mice (n=16) served as control. The surviving animals underwent in vivo MMP-targeted micro-single photon emission computed tomographic/computed tomographic imaging, using RP805, a technetium-99m-labeled MMP-specific tracer, followed by ex vivo planar imaging, morphometry, and gene expression analysis. RP805 uptake in suprarenal aorta on micro-single photon emission computed tomographic images was significantly higher in animals with AAA when compared with angiotensin II-infused animals without AAA or control animals. CD68 expression and MMP activity were increased in AAA, and significant correlations were noted between RP805 uptake and CD68 expression or MMP activity but not aortic diameter. A group of angiotensin II-infused animals (n=24) were imaged at 1 week and were followed up for additional 3 weeks. RP805 uptake in suprarenal aorta at 1 week was significantly higher in mice that later developed rupture or AAA. Furthermore, tracer uptake at 1 week correlated with aortic diameter at 4 weeks. CONCLUSIONS: MMP-targeted imaging reflects vessel wall inflammation and can predict future aortic expansion or rupture in murineAAA. If confirmed in humans, this may provide a new paradigm for AAA risk stratification.
Authors: Femke A M V I Hellenthal; Willem A Buurman; Will K W H Wodzig; Geert Willem H Schurink Journal: Nat Rev Cardiol Date: 2009-06-23 Impact factor: 32.419
Authors: Elliot L Chaikof; David C Brewster; Ronald L Dalman; Michel S Makaroun; Karl A Illig; Gregorio A Sicard; Carlos H Timaran; Gilbert R Upchurch; Frank J Veith Journal: J Vasc Surg Date: 2009-10 Impact factor: 4.268
Authors: Mahmoud Razavian; Jiasheng Zhang; Lei Nie; Sina Tavakoli; Niema Razavian; Lawrence W Dobrucki; Albert J Sinusas; D Scott Edwards; Michael Azure; Mehran M Sadeghi Journal: J Nucl Med Date: 2010-06-16 Impact factor: 10.057